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Abstract: Publication date: Available online 17 November 2018Source: Tetrahedron LettersAuthor(s): Sergey Grintsevich, Alexander Sapegin, Elena Reutskaya, Mikhail Krasavin The tricyclic ring system of the antiviral drug nevirapine has been employed to test the workability of the hydrated imidazoline ring expansion (HIRE) reaction which was previously exemplified for [1.4]oxazepine and [1.4]thiazepine counterparts. The imidazoline nucleus was grafted onto the lactam moiety of nevirapine in two high-yielding steps. Subsequent N-alkylation and the HIRE reaction proceeded as envisioned and delivered rare ring-expanded diarene-fused 1,4,7-triazecines with a diversity of alkyl substituents at the lactam nitrogen atom. These findings extend the scope of the HIRE reaction to the medicinally prominent [1.4]diazepine chemical space.Graphical abstract

Abstract: Publication date: Available online 17 November 2018Source: Tetrahedron LettersAuthor(s): Jozef Gonda, Miroslav Psotka, Miroslava Martinková, Simona Fazekašová, Tatiana Mitríková, Mária Vilková The reaction of (2S,3S,4R)-2,3,4,7-tetrahydroxy-6-oxoheptanals with lower alcohols produced protected 3-deoxy-d-arabino-2-heptulosonates. The key transformation is based on an 1,4-O–O silyl group migration, followed by 6-exo-trig cyclisation to give the final pyranose.Graphical abstract

Abstract: Publication date: Available online 16 November 2018Source: Tetrahedron LettersAuthor(s): Cai-Ling Fan, Kuan Hu, Jing-Lin Wang, Xin-Qi Hao, Jun-Jie Wei, Mao-Ping Song, Chao Zheng An efficient protocol has been accomplished for the synthesis of quaternary α-aminosuccinimides in toluene medium involving 2-phenylimidazo[1, 2-a]pyridine in a one-pot reaction promoted by Ferric Nitrate at 120 oC. The protocol presented herein, is for the first time, via a novel transformation where Ferric Nitrate promotes imidazo[1,2-a]pyridine structural metamorphosis to the title compound quaternary succinimides. High compatibility, easy work-up, and excellent yields are the advantages of this protocol. The quaternary α-aminosuccinimides are expected to have great potential in synthesizing quaternary α-amino acids and applications in medicinal chemistry.Graphical abstract

Abstract: Publication date: Available online 14 November 2018Source: Tetrahedron LettersAuthor(s): Debojit Hazarika, Prodeep Phukan A rapid process for decarboxylative bromination of α,β-unsaturated carboxylic acids have been developed using N,N-dibromo-p-toluenesulfonamide (TsNBr2). Treatment of cinnamic acids with TsNBr2 in presence of potassium carbonate in acetonitrile produces corresponding β-bromostyrenes at room temperature. Exclusive formation of (E)-β-bromostyrenes was observed in a stereoselective manner within a very short period of time (5-15 min). This method was further extended for obtaining 1-bromoalkynes from corresponding propiolic acids. Instantaneous formation of bromoalkynes was observed when the reaction was carried out in presence of DBU as a base in acetonitrile at room temperature. A wide variety of cinnamic acids and propiolic acids could be converted to corresponding β-bromostyrenes and 1-bromoalkynes respectively under mild reaction condition with high to excellent yield.Graphical abstract

Abstract: Publication date: Available online 13 November 2018Source: Tetrahedron LettersAuthor(s): Han-Sem Kim, Sung-Ryu Joo, Ueon Sang Shin, Seung-Hoi Kim A convenient heterogeneous catalytic system consisting of recyclable and reusable carbon nanotube-chitosan nanohybrid film and copper salt was developed for the aerobic ipso-hydroxylation of arylboronic acids. A variety of arylboronic acids bearing electron-withdrawing or electron-donating groups were smoothly transformed at room temperature in water to afford the corresponding phenols in high yields.Graphical abstract

Abstract: Publication date: Available online 13 November 2018Source: Tetrahedron LettersAuthor(s): Zhengjiang Fu, Yongqing Jiang, Ligao Jiang, Zhaojie Li, Shengmei Guo, Hu Cai A simple and practical Cu-catalyzed decarboxylative iodination has been well established under aerobic condition, which provides a useful method to synthesize aryl iodides in moderate to good yields with the use of (hetero)aryl carboxylic acids and NaI as starting materials. Thiabendazole has been prepared via a three-step procedure to show synthetic practicability of the protocol.Graphical abstract

Abstract: Publication date: Available online 13 November 2018Source: Tetrahedron LettersAuthor(s): Bel Youssouf G. Mountessou, Joseph Tchamgoue, Jean Paul Dzoyem, Roland T. Tchuenguem, Frank Surup, Muhammad I. Choudhary, Ivan R. Green, Simeon F. Kouam Two xanthones, 2-(3-hydroxy-3,3-dimethyldihydroallyl)-dihydro-6-deoxyisojacareubin (1) and dihydro-6-deoxyjacareubin (2), and two 3⟶8 rotameric biflavonoids, (2R,3S)-volkensiflavone-7-O-β -acetylglucopyranoside (3) and (2S,3S)-morelloflavone-7-O- β -acetylglucopyranoside (4), together with fifteen known compounds, were isolated from a dichloromethane/methanol (1:1, v/v) extract of the bark of the plant Allanblackia floribunda. The structures of the new compounds were elucidated by NMR spectroscopy and mass spectroscopic techniques and those of the known ones were deduced by comparison with data reported in the literature. The isolated biflavonoids were obtained as mixtures of conformers exhibiting duplicate NMR signals in solution at 25 °C and their respective absolute configurations were assigned using circular dichroism spectroscopy. Selected isolated compounds were assessed for their antibacterial and antioxidant properties.Graphical abstract

Abstract: Publication date: Available online 12 November 2018Source: Tetrahedron LettersAuthor(s): Santoshkumar M. Potadar, Anil S. Mali, Krishnakant T. Waghmode, Ganesh U. Chaturbhuj This is the first-time report on the repurposing n-butyl stannoic acid as a catalyst for direct amidation of carboxylic acids with amines. Notably, efficient amidation observed in comparison with all other catalytic methods reported up until now. The protocol has successfully applied to the synthesis of a variety of amides. Moderate reaction parameters, clean amidation with excellent yields of desired amides, ability to tolerate a variety of functional groups, easy product isolation; commercial availability and recyclability of the catalyst are key advantages of the current protocol.Graphical abstract

Abstract: Publication date: Available online 12 November 2018Source: Tetrahedron LettersAuthor(s): Stefano Federico, Tuhina Khan, Nicola Relitti, Giulia Chemi, Margherita Brindisi, Simone Brogi, Ettore Novellino, Daniela M. Zisterer, Giuseppe Campiani, Sandra Gemma, Stefania Butini We developed a Jocic-type protocol for the construction of the pyrrolonaphthoxazepine (PNOX) core. After an initial investigation based on the isolation of a trichloromethyl carbinol derivative, we shifted our attention towards a multicomponent single-step protocol. Screening of a variety of bases and solvents led to the identification of the optimum conditions for the preparation of the key α-aryloxy carboxylic acids to undergo intramolecular cyclization. The novel chemical route significantly improved overall yields for the preparation of PNOX-based compounds and was successfully extended to the preparation of 1,4-benzoxazinone-based templates.Graphical abstract

Abstract: Publication date: Available online 10 November 2018Source: Tetrahedron LettersAuthor(s): Anthony Romieu, Garance Dejouy, Ibai E. Valverde To expand the range of primary aniline fluorophores available and suitable for the design of fluorogenic protease probes, the synthesis of 3-imino-3H-xanthen-6-amine (known as pyronin) and its silicon analog (Si-pyronin) was explored and presented here. A comprehensive photophysical study of these two fluorescent anilines, confirms the effectiveness of the heteroatom-substitution approach (O→SiMe2) to yield dramatic red-shifts in absorption and fluorescence maxima of the xanthene scaffold (+85 nm). However, it also revealed its adverse effect on the hydrolytic stability of the Si-pyronin, especially at physiological pH. The pro-fluorescent character and utility of these two fluorogenic (hetero)xanthene dyes are also proved by the preparation and in vitro validation of activatable fluorescence “turn-on” probes for penicillin G acylase (PGA).Graphical abstract

Abstract: Publication date: Available online 10 November 2018Source: Tetrahedron LettersAuthor(s): Sitanshu Kumar, Kapil Mukesh, Kusum Harjai, Vasundhara Singh An efficient multicomponent synthesis of Ugi compounds comprising coumarin backbone has been achieved by employing one pot five component sequential Knoevenagel-Ugi reaction. This method offers the advantages of easy handling procedure, atom economy, mild reaction conditions and good yields of products. A molecular library was synthesized by changing the substituents on two of the independent starting materials. The synthesized compounds were also tested for anti-microbial activities and were found to be moderate to good anti-bacterial agents.Graphical abstract

Abstract: Publication date: Available online 10 November 2018Source: Tetrahedron LettersAuthor(s): Robert W. Davis, Alexander Allweil, Jianhua Tian, Alan R. Brash, Gary A. Sulikowski Linoleate triol esters are intermediates along the pathway of formation of the mammalian skin permeability barrier. In connection with the study of their involvement in barrier formation we required access to isomerically pure and defined samples of four linoleate triol esters. A common synthetic strategy was developed starting from isomeric alkynols derived from D-tartaric acid and 2-deoxy-D-ribose.Graphical abstract

Abstract: Publication date: Available online 10 November 2018Source: Tetrahedron LettersAuthor(s): Tiantian Zhang, Hongjin Xu, Chuanjun Song, Junbiao Chang The treatment of bromo homoallyl pyrrolyl/indolyl ketone derivatives with Pd(OAc)2 in the presence of PPh3 and Cs2CO3 in DMF resulted in the formation of tetrahydroindolones and tetrahydrocarbazolones in moderate to good isolated yields.Graphical abstract

Abstract: Publication date: Available online 10 November 2018Source: Tetrahedron LettersAuthor(s): Mozhgan Navidi, Shreya Yadav, Andrey V. Struts, Michael F. Brown, Nasri Nesnas We report the synthesis of 9-CD3-9-cis-retinal via a six-step procedure from β-ionone. The steps involve an initial deuteration of the methyl ketone of β-ionone followed by two consecutive Horner-Wadsworth-Emmons (HWE) coupling reactions and their corresponding DIBAL reductions. A final oxidation of the allylic alcohol of the retinol leads to the target compound. This deuterium labeled retinoid is an important cofactor for studying protein-retinoid interactions in isorhodopsin.Graphical abstract

Abstract: Publication date: Available online 9 November 2018Source: Tetrahedron LettersAuthor(s): Shin-ichiro Kurimoto, Yurika Iinuma, Jun'ichi Kobayashi, Takaaki Kubota A new 12-memberd macrolide, symbiodinolactone A, was isolated from the culture broth of symbiotic marine dinoflagellate Symbiodinium sp. The gross structure of symbiodinolactone A was elucidated by spectroscopic analyses, and the relative configuration was elucidated by the J-based configuration analysis and density-functional theory calculations. Symbiodinolactone A is the new 12-membered macrolide possessing an E double bond between C-4 and C-5, a branched methyl group at C-7, and a 1,2,3-trihydroxybutyl group at C-11. Symbiodinolactone A is the first usual size macrolide and the first non-nitrogen-containing macrolide from dinoflagellate Symbiodinium sp. Symbiodinolactone A might be generated by the unexplained dinoflagellate polyketide biosynthetic machinery.Graphical abstract

Abstract: Publication date: Available online 9 November 2018Source: Tetrahedron LettersAuthor(s): Hideaki Takahashi, Shin-ichiro Kurimoto, Jun'ichi Kobayashi, Takaaki Kubota A new indole alkaloid with the canthin-6-one skeleton, ishigadine A, has been isolated from an Okinawan marine sponge Hyrtios sp. The structure of ishigadine A was elucidated on the basis of spectroscopic analyses. Ishigadine A is a new canthin-6-one alkaloid possessing a hydroxy group, a 1,3-dimethyl-4-methylthioimidazolium, and 1-propylguanidine. Ishigadine A is the third canthin-6-one alkaloid from sponges. Ishigadine A might be generated from L-arginine, L-histidine, and L-tryptophan. Ishigadine A exhibited moderate cytotoxicity against L1210 murine leukemia cells.Graphical abstract

Abstract: Publication date: Available online 8 November 2018Source: Tetrahedron LettersAuthor(s): Andrew Bailey, Andrew Lister, Thomas Moss, James S. Scott, Ye Wu, Scott G. Lamont In the following communication we report two complementary approaches for the synthesis of trans 8-substituted-6-phenyl-6,7,8,9-tetrahydro-3H-pyrazolo[4,3–f]isoquinolines. The first method, directly from α-methyl substituted indazole ethanamines, was successful but had limited substrate scope. The second method utilised a modified Pictet-Spengler cyclisation reaction on an aniline substrate followed by late stage construction of the indazole ring and was more versatile in terms of substrate scope.Graphical abstract

Abstract: Publication date: Available online 8 November 2018Source: Tetrahedron LettersAuthor(s): Martin A. Dolan, Alexandre D.C. Dixon, John D. Chisholm, Daniel A. Clark Ruthenium–catalyzed enyne metathesis is a reliable and efficient method for the formation of 1,3-dienes, a common structural motif in synthetic organic chemistry. The development of new transition-metal complexes competent to catalyze enyne metathesis reactions remains an important research area. This report describes the use of ruthenium (IV) dihydride complexes with the general structure RuH2Cl2(PR3)2 as new catalysts for enyne metathesis. These ruthenium (IV) dihydrides have been largely unexplored as catalysts in metathesis-based transformations. The reactivity of these complexes with 1,6 and 1,7-enynes was investigated. The observed reaction products are consistent with the metathesis activity occurring through a ruthenium vinylidene intermediate.Graphical abstract

Abstract: Publication date: Available online 7 November 2018Source: Tetrahedron LettersAuthor(s): David W. Watson, Matthew Gill, Paul Kemmitt, Scott G. Lamont, Mihai V. Popescu, Iain Simpson 2,6-Lutidine has been identified as a beneficial additive for the oxidative cleavage of olefins to ketones by NaIO4 in the presence of catalytic RuCl3, improving the yield and shortening the reaction times. In the absence of 2,6-lutidine reactions stalled at the diol intermediate with incomplete conversion to the desired ketones. The reaction protocol described herein also avoids the use of harmful solvents such as CCl4 and DCE and is tolerant of a range of functional groups.Graphical abstract

Abstract: Publication date: Available online 7 November 2018Source: Tetrahedron LettersAuthor(s): Renée L. Beyer, Hakan Kandemir, Mohan Bhadbhade, Ibrahim F. Sengul, Chao-wei Leu, Daniel Wenholz, Naresh Kumar, David StC. Black Acylation reactions of 4,6-dimethoxyindoles with glyoxyloyl chlorides were achieved by the use of graphite powder in 1,2-dichloroethane at reflux. The products were monoketones as a result of decarbonylation, rather than the expected 1,2-diketones. Treatment of these monoketones with base led to their cyclisation and elimination of methanol to afford the novel dipyrrolo[2.3-a:1’,2’,3’-fg]acridin-12(1H)-ones.Graphical abstract

Abstract: Publication date: Available online 7 November 2018Source: Tetrahedron LettersAuthor(s): Kyle Clagg, Sara Hold, Archana Kumar, Stefan G. Koenig, Remy Angelaud The direct application of Knochel-Hauser derivative arylmagnesium halides in Kumada-Corriu couplings is described. By utilizing the in situ-generated Grignard reagents, the transmetalation with stoichiometric zinc salts to known Negishi coupling conditions is avoided, thereby streamlining the transformation. Several aromatic hetereocycles participate in the deprotonation and couple with a variety of phenyl iodides and bromides in isolated yields up to 81%. The parent system is demonstrated on 6 g scale with 79% yield, and monitored via ReactIR to show the stability of the Grignard and progression of the deprotonation / C-C coupling reaction.Graphical abstract

Abstract: Publication date: Available online 5 November 2018Source: Tetrahedron LettersAuthor(s): Mohit L. Deb, Bhaskar Deka, Iftakur Rahman, Pranjal K. Baruah Here we report L-proline catalyzed 3-component reaction of indoles, aldehydes and N-substituted anilines in water as solvent at room temperature for the synthesis of 3-(α,α-diarylmethyl)indoles. The reaction is in fact a Michael addition of N-substituted anilines to alkylideneindolenines. The reaction is very clean, high yielding and having broad substrate scope. A tentative mechanism is proposed.Graphical abstract

Abstract: Publication date: Available online 5 November 2018Source: Tetrahedron LettersAuthor(s): Min-Sung Ko, Adil S. Aslam, Dong-Gyu Cho A new tolan derivative was synthesized as a selective ion pair receptor for LiHSO4. The observed ion pair selectivity was accomplished by introducing aza-12-crown-4, which is size-selective for Li+. The ion pair receptor can function as an extractor and fluorescent indicator for LiHSO4.Graphical abstract

Abstract: Publication date: Available online 5 November 2018Source: Tetrahedron LettersAuthor(s): Fei Liu, Yeshen Luo, Meiying Xu A new ratiometric two-photon fluorescence sensor, Qca-Cy2, comprised of a hybrid cyanine–carbazole platform with two rotating sites is described. Qca-Cy2 can report on mitochondrial viscosity within live cells, as well as in living tissues at depths of 50-130 μm by ratiometric fluorescence imaging using two-photon microscopy.Graphical abstractQca-Cy2 is comprised of a hybrid cyanine–carbazole platform with two rotating sites. Qca-Cy2 can report on mitochondrial viscosity within live cells, as well as in living tissues at depths of 50-130 μm by ratiometric fluorescence imaging using two-photon microscopy.

Abstract: Publication date: Available online 5 November 2018Source: Tetrahedron LettersAuthor(s): Ivan Šolić, Hong Xuan Lin, Roderick W. Bates Are reactions employing Lewis acids really catalysed by those Lewis acids, or by “hidden Brønsted acids”, i.e. Brønsted acids generated in situ by hydrolysis? Testing of a series of reactions using Sc(III), Fe(III), In(III) and Y(III) by addition of 2,6-di-t-butyl-4-methylpyridine reveal that all are likely to follow the latter pathway. A reaction claimed to be catalysed by CBr4 through halogen bonding is also likely to be Brønsted acid catalysed.Graphical abstract

Abstract: Publication date: Available online 3 November 2018Source: Tetrahedron LettersAuthor(s): Jonas Verhoeven, B. Narendraprasad Reddy, Lieven Meerpoel, Jan Willem Thuring, Guido Verniest Pyrrolotriazines and related fused azaheterocycles have high potential for the synthesis of bioactive compounds, especially as a purine base isoster in carbon linked nucleosides. Although many structurally related compounds have already been synthesized and used in medicinal chemistry, pyrrolo[1], [3], [5]triazines have barely been described. The present work describes the synthesis of such heterocycles via condensation of 2-amino-3-ethoxycarbonylpyrrole with ethoxycarbonyliso(thio)cyanate. In a brief reactivity study of the obtained fused pyrroles, O- and S-alkylation, ester hydrolysis as well as regioselective bromination at the 6-position was demonstrated.Graphical abstract

Abstract: Publication date: Available online 2 November 2018Source: Tetrahedron LettersAuthor(s): Shoko Mori, Kohtaro Sugahara, Mitsuru Maeda, Keiko Shimamoto, Takashi Iwashita, Tohru Yamagaki Palytoxin (PTX) has been widely studied owing to its outstanding toxic properties and complex structural features. It is a great challenge to identify and isolate analogues of PTX from various organisms and reveal their physiological activities. We previously reported the isolation of PTX as an insecticidal compound from the red alga, Chondria armata. In this study, we investigate another active compound from C. armata, which has similar toxicity and chromatographic behavior as PTX. Our detailed structural analysis reveals that this compound is palytoxin carboxylic acid. We characterized its physicochemical properties and conducted extensive NMR studies. This analogue has a structure devoid of the terminus of PTX, such that its presence in the alga implies the role of symbiotic microorganisms in marine ecosystems.Graphical abstract

Abstract: Publication date: Available online 31 October 2018Source: Tetrahedron LettersAuthor(s): Andreza S. Figueredo, Luis O.B. Zamoner, Martin Rejzek, Robert A. Field, Ivone Carvalho Multivalent carbohydrates, or glycoclusters, are useful tools to study glycan-lectin and glycan-enzyme recognition processes and have wide potential therapeutic applicability. Herein, we report the synthesis of novel glycoclusters presenting glucopyranose units in alternate arrangements by coupling through the C-1, C-2, C-3 or C-6 sugar positions and using tetra- and hexa-valent scaffolds for multivalent display. Coupling the appropriate azide-functionalised d-glucopyranose units with alkynlated penta- or dipenta-erythritol central cores was accomplished via copper-catalysed azide-alkyne cycloaddition (CuAAC), yielding a panel of eight tetra- and hexa-valent glycoclusters in good yields (52-83%). This click chemistry strategy was extended to the preparation of four heteroglycoclusters using a tris(hydroxymethyl)-aminomethane (TRIS) central scaffold. One unit of either the conventional 1-deoxy-d-nojirymicin iminosugar or its’ C-5 epimeric l-gulo isomer, were incorporated along with three d-glucopyranose units linked through either C-1 or C-6.Graphical abstract

Abstract: Publication date: Available online 29 October 2018Source: Tetrahedron LettersAuthor(s): Nobuyuki Mase, Moniruzzaman, Shunsuke Mori, Jun Ishizuka, Fumihiro Kumazawa, Shoji Yamamoto, Kohei Sato, Tetsuo Narumi The synthesis of poly-L-lactide (PLLA) in supercritical carbon dioxide (scCO2) was accomplished using an organocatalyst. The reaction proceeded smoothly under CO2 plasticizing polymerization conditions at a lower temperature than those conventionally employed. This method allowed the formation of high-molecular-weight, pure PLLA, and therefore has the potential to reduce energy consumption and minimize production costs. Our method is non-toxic and efficient, affording a high-quality product while complying with volatile organic compound regulations. We can produce PLLA that meets the increasing standards (safety and high functionality) of the medical sector, while being applicable to full-scale industrial manufacturing and academic research.Graphical abstract

Abstract: Publication date: Available online 28 October 2018Source: Tetrahedron LettersAuthor(s): Bhavna Kaveti, Sandra C. Ramírez-López, Rocío Gámez Montaño The sequential aligning of two eco-friendly and powerful tools for the synthesis of peptidomimetics resulted in the rapid generation of molecular complexity in target molecules. We herein report a versatile IMCR/post-transformation/tandem synthetic strategy that emphasizes the special role of orthogonal bifunctional reagents in isocyanide based multicomponent reactions (IMCR) to generate a synthetic platform for subsequent heterocyclization reactions. This is the first one-pot synthesis of a 2,5-diketopiperazine linked to a 1,4-disubstituted 1,2,3-triazole. The Ugi-4CR/lactamization/click sequence is facile, mild, atom-economical, and green. The present work contributes to the green and one-pot synthesis of bis-heterocycle peptidomimetics and design of new bioactive molecules.Graphical abstract

Abstract: Publication date: Available online 26 October 2018Source: Tetrahedron LettersAuthor(s): Liang Xu, Yingying Chen, Zhenlu Shen, Yuru Wang, Meichao Li An interesting and convenient procedure for the oxidative transformation of aryl alkyl ketones and secondary benzylic alcohols to aryl carboxylic acids has been developed. By using iodine and Fe(NO3)3·9H2O as the catalysts, DMSO and oxygen as the oxidants, the desired aryl carboxylic acids were synthesized in moderate to excellent yields (up to 91%).Graphical abstract

Abstract: Publication date: Available online 26 October 2018Source: Tetrahedron LettersAuthor(s): Bhausaheb N. Patil, Pratima A. Sathe, Babasao S. Parade, Kamlesh S. Vadagaonkar, Atul C. Chaskar Iodine/NaOH-catalyzed one-pot dehomologative oxidation of styrenes to aryl carboxylic acids has been reported. A wide range of carboxylic acids are obtained using iodine (I2) as a catalyst, tert-butyl hydroperoxide (TBHP) as an oxidant and sodium hydroxide (NaOH) as a base. This reliable conversion involves dehomologation of styrene to aromatic aldehyde which on subsequent oxidation affords aryl carboxylic acid. This protocol was used for gram-scale synthesis as it is free from chromatographic purification. This is the first report for the oxidative transformation of styrenes into aryl carboxylic acids under transition metal-free conditions.Graphical abstract

Abstract: Publication date: Available online 25 October 2018Source: Tetrahedron LettersAuthor(s): Hannah R. Dexter, Esther Allen, David M. Williams Pterosin B is a naturally occurring indanone found in bracken fern (Pteridium aquilinum) that displays a variety of interesting pharmacological properties, but for which few stereoselective syntheses exist. Herein we describe a 7-step stereoselective synthesis of (2R)-pterosin B via 6-bromo-5,7-dimethylindan-1-one whose structure was confirmed by NOE analysis and structure determination by X-ray crystallography. The hydroxyethyl chain was introduced via a Suzuki-Miyaura cross-coupling reaction. The 2-methyl group was introduced stereoselectively by methylation of a SAMP [(S)-1-amino-2-methoxymethyl)pyrrolidine] hydrazone and the chiral auxiliary was removed to produce (2R)-pterosin B. The structure of pterosin B was confirmed by specific rotation and structural determination by X-ray crystallography.Graphical abstract

Abstract: Publication date: Available online 25 October 2018Source: Tetrahedron LettersAuthor(s): Sandra Gemma, Luisa di Cerbo, Nicola Relitti, Alessandra Vallone, Margherita Brindisi, Simone Brogi, Giulia Chemi, Ettore Novellino, Giuseppe Campiani, Stefania Butini We developed a synthetic strategy for the preparation of tetrahydrofuro[2,3-c][1,2]dioxane and 2,3,8-trioxa[3,3,1]nonanes bearing polar functional groups at C3 and C4, respectively. The synthetic strategy has been applied to the synthesis of 2,3,8-trioxa[3,3,1]nonanes bearing various amides and amines at C3 useful for structure-activity relationships investigation as antiplasmodial compounds. The synthesis of 1 and the reaction conditions identified for its conversion to amides and amines could pose the basis for the use of this class of endoperoxides also in conjugation with other drugs for polypharmacology approaches.Graphical abstract

Abstract: Publication date: Available online 25 October 2018Source: Tetrahedron LettersAuthor(s): Julien R.C. Prevost, Arina Kozlova, Bouazza Es Saadi, Esra Yildiz, Sara Modaffari, Didier M. Lambert, Lionel Pochet, Johan Wouters, Eduard Dolusic, Raphaël Frédérick Highly functionalized 5-bromo-2-amino-1,3-thiazoles bearing various substituents could be easily prepared by a rapid and efficient one-pot method, using simple starting materials and mild conditions while avoiding the use of metal catalysts or inconvenient reagents such as elemental halogens. These useful products can serve as starting materials for other reactions or as pharmacologically interesting compounds. In our work we have shown that the resulting 5-bromothiazole compounds could lead to monoacylglycerol lipase (MAGL) inhibition in the μM range.Graphical abstractThe present study describes the optimization of a new method of synthesis of highly functionalized 5-bromo-2-amino-1,3-thiazoles by a rapid and efficient one-pot method, using simple starting materials and mild conditions. Interestingly some of the synthesized compounds demonstrate promising monoacylglycerol lipase inhibition properties.

Abstract: Publication date: Available online 25 October 2018Source: Tetrahedron LettersAuthor(s): Helen A. Clement, Dennis G. Hall A Pd-catalyzed borylative migration methodology for cyclic enol perfluorosulfonates was applied to the synthesis of the corresponding 7-membered, azepane ring system. Throughout the optimization, it was shown that the reaction is sensitive to the nitrogen protecting group as well as the type of base and solvent. The resulting cyclic allylboronate reacts stereoselectively with aldehydes for the synthesis of novel α-hydroxyalkyl dehydroazepanes in good yield and enantioselectivity over two steps. We highlight the utility of this methodology with an efficient synthesis of the de novo 7-membered ring analogue of the piperidine alkaloid β-conhydrine.Graphical abstract

Abstract: Publication date: Available online 25 October 2018Source: Tetrahedron LettersAuthor(s): Tara Man Kadayat, Geumwoo Lee, Kyungjin Jung, Hee-Jong Hwang, Jeongmin Joo, Dongyup Hahn, Hayoung Hwang, Keun-Gyu Park, Sung Jin Cho, Kyung-Hee Kim, Jungwook Chin Peroxisome proliferator-activated receptor delta (PPARδ) is considered as a promising biological target for the development of new drugs to treat metabolic syndrome including hyperlipidemia. In this study, a simple and efficient method for the preparation of a unique dimethyl thiazoline containing intermediate (13) of new PPARδ agonists as GW501516 analogue is described. The intermediate 13 was readily obtained by coupling reaction of 4-(chloromethyl)-5,5-dimethyl-2-(4-(trifluoromethyl)phenyl)-4,5-dihydrothiazole (11) with 4-mercapto-2-methylphenol (12) in the presence of tetrabutylammonium hydrogensulfate (TBAHS) and Cs2CO3 in DMF at 80 °C for 1 h. This unique intermediate could be useful for the synthesis of various novel PPARδ agonists to understand the structural and biological significance of PPARδ.Graphical abstract

Abstract: Publication date: Available online 25 October 2018Source: Tetrahedron LettersAuthor(s): Bianca M. Saliba, Satyam Khanal, Michael A. O'Donnell, Kathryn E. Queenan, Junho Song, Matthew R. Gentile, Seann P. Mulcahy Two different pathways for the synthesis of annulated pyrido[3,4-b]indoles are reported using metal-catalyzed cyclotrimerization reactions. A stepwise process using Rh(I)-catalysis in the final step of the synthesis and a multicomponent, tandem catalytic approach using Pd(0)-catalysis both lead to complex nitrogen-containing heterocycles in good yields. Substituent effects are investigated for both pathways, demonstrating that the Pd(0)-catalyzed approach is more sensitive to electron-withdrawing groups.Graphical abstract

Abstract: Publication date: Available online 25 October 2018Source: Tetrahedron LettersAuthor(s): Žiga Jakopin A straightforward route for preparing derivatives of ethyl 5-trichloromethyl-1,2,4-oxadiazole-3-carboxylate, in which the 5-trichloromethyl and/or the ester functionalities are displaced by various nucleophiles, has been designed. Mild reaction conditions were chosen to enable the formation of products, which constitute a new series of bifunctional 3,5-disubstituted 1,2,4-oxadiazole building blocks capable of being integrated into biologically relevant molecules.Graphical abstract

Abstract: Publication date: Available online 24 October 2018Source: Tetrahedron LettersAuthor(s): Si Feng, Liangyuan Yao, Fengliang Liu, Xiao Zeng, Junjie Wang A new family of chiral solvating agents based on chiral didentate amino alcohols and chloromethyl pyridine derivatives were synthesized by ball milling in solvent free condition. The new chiral tridentate amino alcohols were tested as chiral NMR solvating agents for the Ts-derivatives of amino acids, other several acids and pyrazole drugs. For the Ts-derivatives of amino acids studied herein, chiral tridentate amino alcohol 3a could be used for the assignment of the absolute configurations of their racemes through the chemical shift non-equivalences of their CH3 (Ts) protons with certain confidence.Graphical abstract